Most cited article - PubMed ID 30628831
Downregulation of endothelial transient receptor potential vanilloid type 4 channel underlines impaired endothelial nitric oxide-mediated relaxation in the mesenteric arteries of hypertensive rats
Metabolic syndrome (MetS) belongs to the serious health complications expanding in cardiovascular diseases, obesity, insulin resistance, and hyperglycemia. In this study, hypertriacylglycerolemic rats fed a high-fat-fructose diet (HFFD) were used as an experimental model of MetS to explore the effect of tested compounds. Effects of a new prospective pyridoindole derivative coded SMe1EC2 and the natural polyphenol rutin were tested. Endothelial nitric oxide synthase (NOS3) and nuclear factor kappa B (NF-?B) expression were assessed in the left ventricle immunohistochemically and left ventricle activity was monitored in isolated perfused rat hearts. NOS3 activity in the left ventricle decreased markedly as a result of a HFFD. NOS3 expression was upregulated by both substances. NF-?B expression was increased in the MetS group in comparison to control rats and the expression further increased in the SMe1EC2 treatment. This compound significantly improved the coronary flow in comparison to the control group during reperfusion of the heart followed after ischemia. Further, it tended to increase left ventricular systolic pressure, heart product, rate of maximal contraction and relaxation, and coronary flow during baseline assessment. Moreover, the compound SMe1EC2 decreased the sensitivity of hearts to electrically induced ventricular fibrillation. Contrary to this rutin decreased coronary flow in reperfusion. Present results suggest that despite upregulation of NOS3 by both substances tested, pyridoindole SMe1EC2 rather than rutin could be suitable in treatment strategies of cardiovascular disorders in MetS-like conditions.
- MeSH
- Biometry MeSH
- Fructose adverse effects MeSH
- Indoles pharmacology therapeutic use MeSH
- Rats MeSH
- Metabolic Syndrome drug therapy enzymology etiology MeSH
- Myocardium metabolism MeSH
- NF-kappa B metabolism MeSH
- Rats, Wistar MeSH
- Drug Evaluation, Preclinical MeSH
- Pyridines pharmacology therapeutic use MeSH
- Rutin pharmacology therapeutic use MeSH
- Heart drug effects MeSH
- Nitric Oxide Synthase Type III metabolism MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Fructose MeSH
- Indoles MeSH
- NF-kappa B MeSH
- Nos3 protein, rat MeSH Browser
- Pyridines MeSH
- Rutin MeSH
- SMe1EC2 MeSH Browser
- Nitric Oxide Synthase Type III MeSH